Intermediate or high risk for preterm birth Pregnancy and Childbirth
Conditions
Interventions
Participants will be randomised in a 1:1 ratio to receive either Pravastatin or placebo. Randomisation will be performed via the trial database using Sealed Envelope.
Participants randomised to the in
Sponsors
University Hospitals Bristol and Weston NHS Foundation Trust
Eligibility
Sex/Gender
Female
Age
16 Years to 60 Years
Inclusion criteria
Inclusion criteria: 1. Pregnant people with a singleton pregnancy identified as being at high or intermediate risk for PTB according to criteria detailed in the Saving Babies’ Lives Care Bundle (V3), where: 1.1. High risk - at least one of the following: 1.1.1. Previous mid-trimester loss >16 weeks' gestation; 1.1.2. Previous PTB 15mm depth removed, or >1 LLETZ procedure carried out or cone biopsy). 2. Between 16+0- and 20+0 weeks’ gestation at randomisation.
Exclusion criteria
Exclusion criteria: 1. Multiple pregnancy 2. 14 units alcohol/week 8. Past/current liver disease 9. ALT or AST above upper limit of normal (as set by local laboratories), to be taken at the time of screening* 10. Bilirubin above upper limit of normal (as set by local laboratories), to be taken at the time of screening* 11. Creatine Kinase (CK) concentration >5 times upper limit of normal (as set by local laboratories), to be taken at the time of screening 12. Currently breastfeeding 13. Unable to provide informed consent 14. Previously participated in PIONEER 15. Currently taking medicines or groups of medicines that are contraindicated for concomitant use with pravastatin§ * It is acknowledged that the Liver Function Test may include different assessments at different sites, therefore for the purpose of the screening blood test, the term “Liver Function Test” at screening should include measurement of Bilirubin and at least one of ALT or AST. If any of these are above the upper limit of the normal, the person would not be eligible for inclusion in PIONEER, and should have ongoing follow-up according to local policy. § Those taking macrolides should be excluded from PIONEER, however, if a limited course of macrolides are prescribed with the course due to complete prior to 20+0 weeks’ gestation, then it may be possible to recruit to PIONEER following completion of the course of antibiotics (if completion of the course of antibiotics is prior to 20+0).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Gestational age, in days, at birth, measured using patient records. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Maternal and neonatal secondary outcomes: Maternal secondary outcomes: maternal mortality; antenatal infection requiring antibiotics; intrapartum infection requiring antibiotics; development of pre-eclampsia; PPROM; harm to mother from intervention; cervical cerclage; progesterone use; shortest cervical length measured. Neonatal secondary outcomes: Premature birth (categorising <37 weeks' gestation, and <34 weeks gestation); Apgar scores at 1, 5, and 10 minutes of age; admission to Neonatal Intensive Care Unit (NICU); birthweight; early neurodevelopmental morbidity; gastrointestinal and respiratory morbidity; neonatal mortality; infection requiring antibiotics; need for respiratory support; harm to offspring from intervention. Collected from hospital databases following birth and discharge from hospital admission. 2. Mechanism of action of Pravastatin, evaluated using mechanistic studies to assess maternal: 2.1. Cervicovaginal fluid concentrations of inflammatory markers of interest, including IL-8, IL-6, IL-2, MBL, IgG1, IgG3, C3b and C5a; 2.2. Vaginal microbiota profile; 2.3. Serum lipid profile: very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) assessed via NMR metabolomics; and, 2.4. Stool microbiota profile and metabolomics profile. 2.5. Maternal blood inflammatory profile. Samples collected as baseline, 24 weeks' gestation and 28 weeks' gestation. 3. For the offspring of pregnancies for those participants recruited during the first 18 months of the trial only. Assessment of child's cognitive and language development using the Parent Report of Children’s Abilities-Revised (PARCA-R) questionnaire. Questionnaire completed at 2 years corrected age for child. | — |
Countries
England, Scotland, United Kingdom
Contacts
Public ContactTaemi Kawahara
Outcome results
None listed